KC Jambo, Malawi College of Medicine - Defining changes in nasal immunity that favour propensity for pneumococcal colonisation in HIV-infected adults

这种细菌，肺炎链球菌（肺炎球菌），是全世界肺炎相关死亡的主要原因。肺炎球菌存在于鼻子和喉咙后部，通常不会引起疾病，但当条件发生变化时，它会导致危及生命的疾病，如肺炎。肺炎球菌通过呼吸道在人与人之间传播。在欧洲和北美，用肺炎球菌结合疫苗（PCV 13）对儿童进行免疫接种大大降低了社区中肺炎球菌疾病的负担和肺炎球菌的流行率，因为儿童不再感染成人。在马拉维等低收入国家没有观察到类似的影响，因为儿童即使在接种疫苗后仍继续携带肺炎球菌。相反，尽管2011年在马拉维引入PCV 13作为常规儿童疫苗，但接受抗逆转录病毒治疗（ART）的艾滋病毒感染成人中肺炎球菌的患病率仍然很高。接受抗逆转录病毒治疗的HIV感染成人中肺炎球菌的持续存在有可能逆转高收入国家报告的PCV 13的潜在公共卫生益处。接受抗逆转录病毒治疗的艾滋病毒感染成年人是肺炎球菌的避风港，可能会促进细菌在社区中的传播。然而，促进接受抗逆转录病毒治疗的艾滋病毒感染成人中肺炎球菌持续存在的因素仍然未知。我建议招募100名马拉维成年人，其中一半是未感染艾滋病毒的，另一半是未经抗逆转录病毒治疗的艾滋病毒感染者。我将从所有研究参与者的鼻子中收集样本，并随访12个月。我将量化一个人被发现鼻子里有肺炎球菌的次数，并在研究组之间进行比较。我还将研究研究组之间鼻子免疫参数的差异。这种比较还将集中在鼻子中免疫参数的变化与个体在鼻子中发现肺炎球菌的次数之间的关系。这将产生关于使接受抗逆转录病毒治疗的艾滋病毒感染成年人更容易感染肺炎球菌的一些因素的信息。此外，我将在实验室中培养从HIV感染者和未感染者的鼻子中获得的细胞，以更深入地了解它们如何与肺炎球菌相互作用。我预计，这项研究将提高目前的理解，为什么肺炎球菌是持续存在于艾滋病毒感染的成人ART。这项工作将允许选择最佳的治疗艾滋病毒和最佳的疫苗接种策略对肺炎球菌，这可能会显着影响肺炎球菌的传播和疾病的高传播设置。

The bacterium, Streptococcus pneumoniae (pneumococcus), is the major cause of pneumonia-related deaths worldwide. The pneumococcus resides in the nose and at the back of the throat, where it does not normally cause disease, but when conditions change it causes life-threatening illness, such as pneumonia. The pneumococcus is transmitted from person to person via the respiratory route. In Europe and North America, immunisation of children with the pneumococcal conjugate vaccine (PCV13) has greatly reduced the burden of pneumococcal disease and prevalence of the pneumococcus in the community because children no longer infect adults. Similar impact has not been observed in low income countries, such as Malawi, because children continue to carry pneumococci even after vaccination. Instead, the prevalence of the pneumococcus among HIV-infected adults on antiretroviral therapy (ART) has remained high despite the introduction of PCV13 as routine childhood vaccine in Malawi in 2011. Persistence of pneumococcus among HIV-infected adults on ART threatens to reverse the potential public health benefits of PCV13 that have been reported from high income countries. HIV-infected adults on ART serve as a haven for pneumococcus and may promote transmission of the bacterium in the community. However, the factors that promote persistence of pneumococcus among HIV-infected adults on ART are still unknown. I propose to recruit 100 Malawian adults, of which half will be HIV-uninfected and the other half will be ART-naïve HIV-infected. I will collect samples from the nose from all study participants and follow them up for 12months. I will quantify the number of times an individual is found with the pneumococcus in their nose, and compare this between the study groups. I will also investigate differences in immune parameters in the nose between the study groups. This comparison will also focus on relating the changes in the immune parameters in the nose with the number of times an individual is found with the pneumococcus in their nose. This will generate information on some of the factors that make HIV-infected infected adults on ART more susceptible to the pneumococcus. Furthermore, I will grow cells obtained from the nose of HIV-infected and uninfected adults in laboratory to generate a deeper understanding of how they interact with pneumococcus. I anticipate that this research study will will improve current understanding of why the pneumococcus is persistently found among HIV-infected adults on ART. This work will allow choices in optimal therapy against HIV and optimal vaccination strategies against pneumococcus, that could significantly impact pneumococcal transmission and disease in high transmission settings.